CN107929717A - A kind of pharmaceutical composition of siramesine and snake venom cytotoxin CTX1 - Google Patents
A kind of pharmaceutical composition of siramesine and snake venom cytotoxin CTX1 Download PDFInfo
- Publication number
- CN107929717A CN107929717A CN201711249967.3A CN201711249967A CN107929717A CN 107929717 A CN107929717 A CN 107929717A CN 201711249967 A CN201711249967 A CN 201711249967A CN 107929717 A CN107929717 A CN 107929717A
- Authority
- CN
- China
- Prior art keywords
- ctx1
- sira
- cell
- pharmaceutical composition
- siramesine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Marine Sciences & Fisheries (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to technical field of pharmaceuticals, more particularly, to the pharmaceutical composition and its application in antitumor drug is prepared of a kind of siramesine and snake venom cytotoxin CTX1.Sira is sigma2 receptor stimulating agents, and Sira causes lysosome membrane permeability to increase inducing death of neoplastic cells after being combined with sigma2 acceptors, Sira can also raise tumour cell lysosome pH value, cause ROS to raise, active cell programmed cell death.Sira is combined with CTX1, strengthen the effect that CTX1 acts on lysosome, and dosages of the CTX1 in pharmaceutical composition is only the 1/3.6~1/2.3 of independent dosage, composition has stronger cooperative effect, killing tumor cell effect significantly improves, and also has significant lethal effect for drug resistant tumour cell.Since drug dose is relatively low, side effect and adverse reaction rate during medication can reduce, and reduce treatment cost, mitigate the financial burden of patient.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, more particularly, to a kind of siramesine and the medicine of snake venom cytotoxin-CTX1
Compositions and its application in antitumor drug is prepared.
Background technology
In snake venom secreted by naja atra Cantor (Naja naja atra) containing various kinds of cell toxin (Cytotoxin,
CTX).From China mainland and Taiwan production Zhoushan cobra venom at least it is separated go out 5~7 kinds of different CTX, for by 60~
The strong basicity polypeptide containing a large amount of hydrophobic residues of 63 amino acid residue compositions, relative molecular mass is 6000~7000Da.
CTXs belongs to three finger toxin family (three-finger toxins), its 4 highly conserved disulfide bond cause the space of CTX
For structure in " three refer to " shape, three finger finger tips are hydrophobic amino acid, refer to side and carry arginine, the lysine of positive charge, and think
This both sexes finger is conducive to CTXs and is combined with cell membrane, and CTXs penetration cells film enters is applied directly to lyase into the cell
Acted on body film, it is in spot distribution that CTXs, which can penetrate lysosome,.The damage of the cancer cell of CTXs mediations is molten by destroying
Enzyme body and realize.Research in recent years finds that lysosome release under dead signal effect is more based on cathepsin
Kind hydrolase, this cathepsin, which is released into kytoplasm, can cause the change of a series of signal path, and participation includes autophagy and withers
Cell death including dying.Naja atra Cantor cytotoxin 1 (cytotoxin 1, CTX1) is this seminar from naja atra Cantor
Separate what μ was purified in poison.CTX1 is by the residual micromolecule polypeptide formed of 60 amino acid, molecular mass 6698Da, ammonia
Base acid sequence is LKCNKLIPIA SKTCPAGKNL CYKMFMMSDL TIPVKRGCID VCPKNSLLVKYVCCNTDRCN.This
Patented technology inventor has found that CTX1 can induce apoptosis and the necrosis of kinds of tumor cells, especially in the experimental study of early period
There is obvious lethal effect to drug resistant breast carcinoma cell strain MCF7, human acute myeloid leukemia cell line KG1a etc., and can
Significantly inhibit the growth of nude mice MCF-7 transplantable tumors；And to a variety of normal cells (such as human bronchial epithelial cell 16HBE, Mouse Bone
The mononuclearcell of marrow, mammary gland normal cell etc.) toxic action is relatively low, and CTX1 to tumour cell there is obvious selectivity to kill
Wound acts on.Experimental result shows that CTX1 handles MCF-7 cells 1h, you can causes the damage of MCF-7 Cytolysosome films, causes
LMP (Lysomal membrane permeability), the ROS in KG1a cells are also significantly raised.CTX1 causes MCF-7 etc.
The death of tumour cell meets the cell death pathways of lysosome mediation, and lysosome is probably the target cell of CTX1 cytotoxicities
One of device, mitochondrial oxidation stress may participate in the MCF-7 process of cell death of CTX1 inductions.
The apoptosis by caspase mediation that tumour cell induces conventional treatment model often obtains
Drug resistance.Therefore, the medicine for the treatment of of cancer is failed to make one the needs met.Lysosome be intracellular most abundant organelle it
One, it participates in the adjusting of cell multiple functions, to maintaining Cell Homeostasis to have key effect.The tumour cell of high malignancy and swollen
There are substantial amounts of lysosome in knurl stem cell, the lysosome increasing number in cell, lysosomal enzyme (including cathepsin)
It is one of characteristic change of tumour cell that expression increase, increased activity, turn-over capacity, which change, and the stable state of tumour cell is also high
Degree depends on effective lyase body function.Therefore, the cell death of change and lysosome induction of the tumour cell to lysosome
Sensitiveness significantly improve.Widened lysosome system makes tumor cell ratio normal cell be easier to be subject to close lysosome medicine
Attack, the close lysosome factor is probably the anti-tumor medicine with high selectivity.Therefore, it is probably for the therapy of lysosome
Treat the up-and-coming new strategy of malignant tumour.Research is found, on many different types of tumour cell sigma2 acceptors
Adjust, and the ligand of sigma2 acceptors it is capable of inhibiting cell breed and induce the programmed death of tumour cell, show sigma2 acceptors
Ligand may strengthen the activity of antitumor drug.International Patent Publication WO 92/22554, which is once described, can be used for treating a variety of essences
God and a series of sigma receptors ligands of neurological disorder, Sira is one of which.There is research to point out that LMP is sigma2 acceptors
The earliest events of ligand inducing death of neoplastic cells, also studies have found that Sira can raise tumour cell lysosome pH value, lead
ROS (Reactive oxygen species) rises are caused, mitochondrial membrane stability are influenced, so that active cell programmed cell death.
Sira early stages are studied as antianxiety and antidepressant class piperidines medicine, and Sira toxicity is found in clinical test
It is relatively low and there is good tolerability, but the effect of corresponding, is not obtained to mental patient.And Sira is to the new of tumour cell
Effect and be subject of the present invention with the new opplications of CTX1 drug combinations.
The content of the invention
It is an object of the invention to provide a kind of antineoplastic pharmaceutical compositions containing snake venom cytotoxin-CTX1, dropping
While the dosage and its toxic side effect of mitigation of low snake venom cytotoxin-CTX1, the anti-of snake venom cytotoxin-CTX1 is given full play to
Tumor function.By the siramesine use in conjunction of the snake venom cytotoxin-CTX1 of low concentration and low concentration, after the results show medication
Have significant synergistic function to the growth inhibition of MCF7 tumor lines, can effectively induce MCF7 cells occur late apoptic and
Necrosis.
The object of the present invention is achieved like this：
A kind of siramesine (Siramesine, Lu-28-179, Sira) and the drug regimen of snake venom cytotoxin-CTX1
Thing.Pharmaceutical composition of the present invention includes CTX1 and siramesine.
Preferably, the amount ratio of the material of A and B is 0.35~1.41:1.
Alternatively, described pharmaceutical composition also includes pharmaceutically acceptable carrier or auxiliary material.
The invention further relates to purposes of the pharmaceutical composition in anti-tumor drug is prepared.
Alternatively, the pharmaceutical composition of the siramesine and snake venom cytotoxin-CTX1 include pharmaceutically acceptable
Carrier or auxiliary material.
Alternatively, the pharmaceutical composition of the siramesine and snake venom cytotoxin-CTX1 by being after drug administration by injection
Drug effect can be played, therefore is prepared as injection, the injection includes parenteral solution, freeze drying powder injection.
Compared with prior art, pharmaceutical composition of the present invention has the following advantages that and marked improvement：Sira is
Sigma2 receptor stimulating agents, Sira cause lysosome membrane permeability to increase (Lysosomal after being combined with sigma2 acceptors
Membrane Permeabilization, LMP) inducing death of neoplastic cells, Sira can also raise tumour cell lysosome PH
Value, causes ROS (Reactive oxygen species) to raise, active cell programmed cell death.Sira is combined with CTX1, is strengthened
CTX1 acts on the effect of lysosome, and dosages of the CTX1 in pharmaceutical composition be only the 1/3.6~1/ of independent dosage
2.3, composition has stronger cooperative effect, and killing tumor cell effect is significantly improved, also had for drug resistant tumour cell aobvious
The lethal effect of work.Since drug dose is relatively low, side effect and adverse reaction rate during medication can reduce, reduce treatment into
This, mitigates the financial burden of patient.
Brief description of the drawings
The lethal effect of Fig. 1 .CTX1 joint groups and single medicine group to MCF7
Note：1.5 μM of VEH=Vehicle, Sira=Sira
***p<0.001, * * p<0.01, * p<The mono- medicine groups of 0.05vs CTX1
Fig. 2 .CTX1 joints Sira acts on the survival rate of MCF7
Note：1.5 μM of FM=Fullmedium, Sira=Sira
***p<0.001, * * p<0.01, * p<The mono- medicine groups of 0.05vs CTX1
Fig. 3 .CTX1 joints Sira acts on the apoptosis mode of MCF7
Note：0.045=CTX10.045 μM, 0.09=CTX10.09 μM, 0.18=CTX10.18 μM, Sira=Sira
1.5μM
Fig. 4 .CTX1 combine the influence that Sira produces MCF7 cells active oxygen ROS
Note：1.5 μM of FM=Fullmedium, Sira=Sira；
**P<0.01, * P<The mono- medicine groups of 0.05vs CTX1
Fig. 5 .CTX1 combine the influence that Sira produces MCF7 cells active oxygen ROS
Influence when Fig. 6 .CTX1 combine Sira inducing cell deaths to mitochondrial membrane potential change
A. the change of mitochondrial membrane potential when various dose CTX1 combines Sira inducing cell deaths
The change (1h, 2h) of different time points mitochondrial membrane potential when B.CTX1 combines Sira inducing cell deaths
Note：**p<0.01, * p<The mono- medicine groups of 0.05vsCTX1；1.5 μM of Sira=Sira
Fig. 7 .CTX1 joints Sira acts on the change of MCF7 post-lysosomes
Note：C=CTX10.135 μM, 1.5 μM of Sira=Sira
***p<The mono- medicine groups of 0.001vs CTX1
Embodiment
Embodiment 1：CTX1 combines influences of the Sira to MCF7 cell growths
After CTX1 joint Sira processing MCF7 cells 12,24 and 36h, the results show that joint group medicine group more mono- than CTX1
Have the function that more obviously to suppress MCF7 cell Proliferations, and inhibitory action has obvious dosage effect and time effect, with
Control group compares with significant significant difference (P ﹤ 0.01), the result is shown in Figure 1.
Embodiment 2：CI values evaluate drug synergism：
The index of cooperation CI values of CTX1 joints Sira show stronger synergistic effect (+++) knot between 0.3~0.7
Fruit is shown in Table 1.And control drug Yi Sha is concentrated mainly on than the CI values of ketone (Ixabepilone, IXA) joint hydroxychloroquine (HCQ)
Between 0.85~3.3, show it is weaker or without synergistic effect (being shown in Table 2,3).
Table 2.IXA combines the HCQ-30 μM of CI value for acting on MCF7N=3)
Table 3.IXA combines the HCQ-40 μM of CI value for acting on MCF7N=3)
Embodiment 3：CTX1 combines influences of the Sira to MCF7 cell deaths
Flow cytometry：CTX1 can significantly induce MCF-7 cell deaths.As CTX1 dosage increases, MCF7 cells
The death rate is significantly raised；The joint group medicine group death rate more mono- than CTX1 raises to obtain more notable (P<0.05), and with late apoptic
Based on necrosis increase, early apoptosis change unobvious.By taking CTX10.18 μM of group as an example, the mono- medicine group cell late apoptic rates of CTX1
For (33.9 ± 7.61) %, necrosis rate is (12.33 ± 7.6) %, and early apoptosis rate is (4.07 ± 2.05) %；CTX1+
Sira joint group cell late apoptics rate is (38.57 ± 1.37) %, and necrosis rate is (35.53 ± 1.01) %, and early apoptosis
Rate is (0.9 ± 0.1) %.See Fig. 2,3.
Embodiment 4：The change of active oxygen ROS during CTX1 joint Sira inducing cell deaths
Flow cytometry is found after marking ROS with probe CM-H2DCFDA, and CTX1 joints Sira acts on MCF724h
After cause ROS significantly to raise, with the increase of CTX1 dosage, ROS caused by drug combination group is significantly raised, with the mono- medicine groups of CTX1
Compared to significant difference (P<0.05) (Fig. 4,5), prompt ROS to combine Sira induction MCF7 cell deaths in CTX1
Certain effect has been played in journey.
Embodiment 5：The change of mitochondrial membrane potential during CTX1 joint Sira inducing cell deaths
MCF7 cell fluorescence intensities after being dyed using Flow cytometry JC-1, the results show：The mono- medicine groups of CTX1 and connection
Processing cell 1h, 2h are combined, percentage shared by the cell with red fluorescence is decreased obviously, and 2h more obvious than 1h declines, with
Exemplified by CTX10.135 μM of group, percentage shared by the cell with red fluorescence is respectively during 1h：CTX1 (81.23 ± 1.58) %,
CTX1+Sira (77.3 ± 0.56) %, and solvent control group is (99.53 ± 0.12) %；Cell institute with red fluorescence during 2h
Accounting for percentage is respectively：CTX1 (73.3 ± 7.57) %, CTX1+Sira (48.54 ± 0.27) %, solvent control group are (97.17
± 1.5) %.Under percentage shared by the mono- medicine groups of CTX1 and cell of the joint group with red fluorescence is with the increase of CTX1 dosage
Drop, joint group have significant difference (P compared with the alone medicine groups of CTX1<0.05) (Fig. 6 A, B).
Embodiment 6：CTX1 combines influences of the Sira to Cytolysosome
MCF7 cell fluorescence intensities after being dyed using Flow cytometry AO, observation CTX1 joint Sira inductions MCF7 are thin
The situation of change of cytolysosome.The results are shown in Figure 7：The mono- medicine groups of CTX1 and joint group processing cell 6h, 12h, band red fluorescence
Cell shared by percentage be decreased obviously, and 12h declines obvious than 6h, and drug combination group medicine group more mono- than CTX1 declines obvious.Medicine
Percentage shared by the cell with red fluorescence is respectively when thing handles 6h：CTX1 (90.3 ± 0.18) %, CTX1+Sira (84.93
± 0.78) %；And solvent control group is (98.13 ± 0.9) %.Percentage shared by cell with red fluorescence during drug-treated 12h
Rate is respectively：CTX1 (53.6 ± 1.2) %, CTX1+Sira (46.47 ± 1.96) %, solvent control group for (99.8 ±
0.06) %.
Claims (5)
- A kind of 1. pharmaceutical composition of siramesine and snake venom cytotoxin-CTX1.
- 2. the pharmaceutical composition of siramesine as claimed in claim 1 and snake venom cytotoxin-CTX1, it is characterised in that：Institute The ratio for stating the amount of snake venom cytotoxin-CTX1 and siramesine material is 0.35~1.41:1.
- 3. as claim 1 state siramesine and snake venom cytotoxin-CTX1 pharmaceutical composition, it is characterised in that：Bag Containing pharmaceutically acceptable carrier or auxiliary material.
- 4. as claim 1 state siramesine and snake venom cytotoxin-CTX1 pharmaceutical composition, it is characterised in that：Institute It is injection to state pharmaceutical composition, and the injection includes parenteral solution, freeze drying powder injection.
- 5. the pharmaceutical composition of any siramesine and snake venom cytotoxin-CTX1 as described in Claims 1 to 4 is anti-in preparation Application in tumour medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711249967.3A CN107929717B (en) | 2017-12-01 | 2017-12-01 | Pharmaceutical composition of siramesine and snake venom cytotoxin-CTX 1 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711249967.3A CN107929717B (en) | 2017-12-01 | 2017-12-01 | Pharmaceutical composition of siramesine and snake venom cytotoxin-CTX 1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107929717A true CN107929717A (en) | 2018-04-20 |
| CN107929717B CN107929717B (en) | 2020-10-02 |
Family
ID=61948286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711249967.3A Active CN107929717B (en) | 2017-12-01 | 2017-12-01 | Pharmaceutical composition of siramesine and snake venom cytotoxin-CTX 1 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107929717B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5232911A (en) * | 1990-01-03 | 1993-08-03 | Ventech Research Inc. | Mixture of a non-covalent heterodimer complex and a basic amphiphatic peptide as cytotoxic agent |
| CN1893947A (en) * | 2003-12-19 | 2007-01-10 | H·隆德贝克有限公司 | Use of siramesine in the treatment of cancer |
| CN101717441A (en) * | 2009-12-04 | 2010-06-02 | 广州医学院 | Venin-sourced demulcent CTXn, and purification method and applications thereof |
| CN101717439A (en) * | 2009-12-04 | 2010-06-02 | 广州医学院 | Venin-derived cytotoxin CTXn for drug rehabilitation and purification method and application thereof |
| CN101926980A (en) * | 2009-07-29 | 2010-12-29 | 中山大学 | Application of cytotoxin (CTX1) from snake venom to preparation of medicament for rehabilitating |
| CN102526704A (en) * | 2012-01-19 | 2012-07-04 | 广州医学院 | Application of snake venom-sourced cytotoxin-CTX1 to preparation of acute leukemia resisting medicine |
| WO2016184855A1 (en) * | 2015-05-19 | 2016-11-24 | Università degli Studi di Parma | New amino acid sequences with microbicidal activity derived from naja atra cardiotoxin 1 (ctx-1) |
-
2017
- 2017-12-01 CN CN201711249967.3A patent/CN107929717B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5232911A (en) * | 1990-01-03 | 1993-08-03 | Ventech Research Inc. | Mixture of a non-covalent heterodimer complex and a basic amphiphatic peptide as cytotoxic agent |
| CN1893947A (en) * | 2003-12-19 | 2007-01-10 | H·隆德贝克有限公司 | Use of siramesine in the treatment of cancer |
| CN101926980A (en) * | 2009-07-29 | 2010-12-29 | 中山大学 | Application of cytotoxin (CTX1) from snake venom to preparation of medicament for rehabilitating |
| CN101717441A (en) * | 2009-12-04 | 2010-06-02 | 广州医学院 | Venin-sourced demulcent CTXn, and purification method and applications thereof |
| CN101717439A (en) * | 2009-12-04 | 2010-06-02 | 广州医学院 | Venin-derived cytotoxin CTXn for drug rehabilitation and purification method and application thereof |
| CN102526704A (en) * | 2012-01-19 | 2012-07-04 | 广州医学院 | Application of snake venom-sourced cytotoxin-CTX1 to preparation of acute leukemia resisting medicine |
| WO2016184855A1 (en) * | 2015-05-19 | 2016-11-24 | Università degli Studi di Parma | New amino acid sequences with microbicidal activity derived from naja atra cardiotoxin 1 (ctx-1) |
Non-Patent Citations (6)
| Title |
|---|
| CHANG, L. S.等: "CAA90962.1", 《GENBANK》 * |
| MINYAN WU等: "The Anticancer Effect of Cytotoxin 1 from Naja atra Cantor Venom is Mediated by a Lysosomal Cell Death Pathway Involving Lysosomal Membrane Permeabilization and Cathepsin B Release", 《THE AMERICAN JOURNAL OF CHINESE MEDICINE》 * |
| STINE S. JENSEN等: "Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo", 《BMC CANCER》 * |
| 刘亚敏: "舟山眼镜蛇细胞毒素CTX1诱导HL-60和KG1a死亡机制的研究", 《万方数据学位》 * |
| 吴敏燕: "舟山眼镜蛇细胞毒素CTX1抗肿瘤作用及机制", 《万方数据学位》 * |
| 梅勇: "舟山眼镜蛇细胞毒素CTX1对人骨肉瘤细胞增殖及凋亡影响的实验研究", 《万方数据学位》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107929717B (en) | 2020-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102357100A (en) | Anti-tumor combination medicament | |
| JP6209579B2 (en) | Pharmaceutical composition that is regarded as a supplementary medicine | |
| CN104398526B (en) | The application of triptolide and Celastrol in antineoplastic is prepared | |
| CN104800858B (en) | HSP90 suppresses peptide conjugate and its application in oncotherapy | |
| EP1549329B1 (en) | Extract with anti-tumor and anti-poisonous activity | |
| Yang et al. | Anticancer activity in vitro and biological safety evaluation in vivo of Sika deer antler protein | |
| Harstrick et al. | Comparison of the antitumor activity of cisplatin, carboplatin, and iproplatin against established human testicular cancer cell lines in vivo and in vitro | |
| CN108743964A (en) | A kind of Brain targeting nucleic acid delivery vector of rabies virus glycoprotein-derived peptide modification and its application | |
| CN105380956B (en) | A kind of pharmaceutical composition of Dana Delany containing Chinese mugwort for treating leukaemia and application | |
| CN107929717A (en) | A kind of pharmaceutical composition of siramesine and snake venom cytotoxin CTX1 | |
| CN101791363B (en) | Broad spectrum anticancer vegetable drug, preparation method and application thereof | |
| US10441564B2 (en) | Fructose analogs and their combinations as anti-cancer agents | |
| CN110075106A (en) | A kind of anti-tumor drug and isoniazid application in preparation of anti-tumor drugs | |
| CN109568313A (en) | A kind of antineoplastic combination drug and its preparing the application in anticancer drug | |
| TWI811478B (en) | Preparation method and pharmaceutical composition for the extract and composition of antrodia cinnamomea. | |
| RU2308285C2 (en) | Agent based on polysaccharides from calamus root enhancing of anti-tumor and anti-metastasis activity of cytostatic preparations | |
| US11167002B2 (en) | Pharmaceutical composition for the treatment of malignant neoplasms including sarcoma, cancers of liver, lung, bladder, blood and cervical, treatment of infectious diseases and type 2 diabetes | |
| CN115177620A (en) | Application of seolonide or pharmaceutically acceptable salt thereof in preparation of medicine for preventing or treating follicular lymphoma | |
| CN107737333A (en) | The pharmaceutical composition of 4 amino quinoline derivatives and snake venom cytotoxin CTX1 | |
| TW201808316A (en) | Use of compositions of water/alcohol extracts of Antrodia cinnamomea cut-log cultivated fruiting body and solid-state cultivated mycelium as auxiliaries for anti-cancer agents | |
| CN103054802A (en) | Procationic/ cationic liposome curcumin preparation for interventional treatment of hepatic carcinoma and preparation method of preparation | |
| TW202206090A (en) | Astragalus pharmaceutical composition enhances the use of cancer treatment | |
| CN108992463A (en) | A kind of composition and pharmaceutical preparation for treating lung cancer | |
| Pereira et al. | The blood-testis barrier as a target of some chemotherapeutic agents | |
| US20060177520A1 (en) | Compositions and methods for reducing cytotoxicity and inhibiting angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Dong Weihua Inventor after: Xiang Yongxin Inventor after: Kong Tianhan Inventor after: Wang Han Inventor after: Peng Xiang Inventor after: Wang Shengsong Inventor before: Dong Weihua Inventor before: Xiang Yongxin Inventor before: Kong Tianhan Inventor before: Wang Han Inventor before: Peng Xiang Inventor before: Wang Shengsong |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230314 Address after: No. 19, Hongji Avenue, Qishan Town, Qimen County, Mount Huangshan City, Anhui Province, 245000 Patentee after: HUANGSHAN SANQI BIOMEDICINE TECHNOLOGY CO.,LTD. Address before: 245000 Floor 1, Qihong Construction Engineering Building, Hongji Avenue, Qishan Town, Mount Huangshan City, Anhui Province Patentee before: HUANGSHAN SANQI BIOMEDICINE TECHNOLOGY CO.,LTD. |